A panel of diverse monoclonal anti-H(PR8) antibodies were produced by somatic cell hybridization. Antigenic variants of A/PR/8/34(HON1) were selected by means of 6 hybridoma antibodies of which 3 delineated H(PR8) specific and 3 HO/H1 crossreactive determinants. The frequency of antigenic variants per individual determinant in cloned parental virus preparations was in the average 10 to the minus 6th power per infectious unit of parental virus. A minimum of 4 (groups of) H determinants that mutated independently from each other could be evidenced by antigenic analysis of the variants selected with the 6 distinct hybridoma antibodies. The comparison by peptide mapping and antigenic analysis of parental and 12 variant H molecules (selected with a H(PR8) specific antibody) was consistent with the concept that variants selected with monoclonal antibodies represent in general single point mutants of the parental virus.